A major difficulty in neurobiology is identifying functional neuronal pathways. Classical anatomical tracing techniques allow gross connectivity between brain regions to be determined. However, critical aspects of information storage and processing presumably reflect the activation of specific subpopulations of neurons in a given brain region in response to a given conjunction of sensory inputs. This project seeks to develop a system in transgenic mice that would allow the permanent marking of neurons that were active in a given brain region within a given time frame. The neurons would be marked with proteins that allow detection of the axonal projections of the marked neurons. In addition, any transgenically expressed protein could be targeted to these neurons. Finally, the relative level of circuit reactivation under various behavioral contingencies could also be examined with this system. The mice developed would have broad utility in studies of neuronal processing both in the study of normal brain function and in disease models.